Predictors of response to remdesivir in GS-5773 COVID-19 study
22 July 2020. Related: Conference reports, COVID-19: investigational drugs, COVID-19, IAS COVID-19 virtual 2020.
Simon Collins, HIV i-Base
Kristen Marks, from Weill Cornell Medicine presented results on predictors of response from patients in a substudy of GS-5773, comparing 5 vs 10-days of remdesivir in severe COVID-19. In practice, participants used remdesivir for a range of days in each arm and because the 5-day arms was as effective as 10-days, results from both arms were combined in this analysis. [1]
The 5773 study enrolled 397 participants, at 55 sites in 8 countries, most from the US (n=229), Italy (n=77) and Spain (n=61).
Endpoints included time to clinical improvement and all-cause mortality, both at day 14.
Baseline characteristics included 168 (42%) ≥65 years old, 144 (36%) female, 276 (70%) white, 45 (11%) Asian, and 44 (11%) Black. Overall, 122 patients (31%) were on high-grade oxygen support (including invasive mechanical ventilation (3%) and non-invasive positive pressure ventilation or high-flow nasal cannula (27%), with 220 (55%) on low-grade oxygen support. Comorbidities were reported as common (50% hypertension, 22% diabetes) and median BMI was 28.7 kg/m2 (range: 16 to 63).
After median follow-up of 10 days (range: 1 to 33 days), 256/397 patients had ≥2-point improvement in the 7-point ordinal scale (from 1=death to 7= not hospitalised) and 44 died.
In a multivariable analysis, baseline factors significantly positively associated with ≥2-point clinical improvement or mortality are included in Table 1. Treatment duration (5 vs 10 days) was not significant for either endpoint.
Racial differences were also included in a poster at the conference. [2]
Table 1: Baseline characteristics associated with clinical outcomes
| Baseline factors in multivariate analysis | HR (95%CI) |
p-value |
| Factors with >2 point improvemen | ||
| Lower grade respiratory support (low-flow oxygen or room air) | 2.16 (1.50 to 3.10) |
p<0.0001 |
| Age <65 | 1.91 (1.46 to 2.55) |
p<0.0001 |
| Black race vs Asian | 3.80 (2.28 to 6.35) |
p<0.0001 |
| White vs Asian | 2.45 (1.60 to 3.76) |
p<0.0001 |
| Outside Italy (likely linked to time period of enrolment) | 1.59 (1.07 to 2.37) |
p<0.0225 |
| No concomitant biologic medication use (ie IL-6, IFN etc) | 2.70 (1.49 to 4.88) |
p<0.0010 |
| Factors associated with increased risk all-cause mortality | ||
| High-grade oxygen support | 5.47 (2.74 to 10.90) |
p<0.0001 |
| history of COPD | 3.41 (1.30 to 8.94) |
p<0.0125 |
| age ≥65y | 2.30 (1.18 to 4.47) |
p<0.0139 |
References
- Marks K et al. Baseline characteristics associated with clinical improvement and mortality in hospitalized patients with severe COVID-19 treated with remdesivir. Track B, Oral abstract.
https://cattendee.abstractsonline.com/meeting/9307/Presentation/4287 - HA not funny et al. Yes, try finding anything on the website. Many posters are listed for remdesivir but they might as well be written with magic dust.
https://goodluckfindingthis/this_is_important_science